| 1. |
- Apps, Richard, et al.
(författare)
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Cerebellar Modules and Their Role as Operational Cerebellar Processing Units
- 2018
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Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4222. ; 17:5, s. 654-682
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Tidskriftsartikel (refereegranskat)abstract
- The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject. Starting with an historical perspective indicating that the basis of the modular organization is formed by matching olivocorticonuclear connectivity, this is followed by consideration of anatomical and chemical modular boundaries, revealing a relation between anatomical, chemical, and physiological borders. In addition, the question is asked what the smallest operational unit of the cerebellum might be. Furthermore, it has become clear that chemical diversity of Purkinje cells also results in diversity of information processing between cerebellar modules. An additional important consideration is the relation between modular compartmentalization and the organization of the mossy fiber system, resulting in the concept of modular plasticity. Finally, examination of cerebellar output patterns suggesting cooperation between modules and recent work on modular aspects of emotional behavior are discussed. Despite the general consensus that the cerebellum has a modular organization, many questions remain. The authors hope that this joint review will inspire future cerebellar research so that we are better able to understand how this brain structure makes its vital contribution to behavior in its most general form.
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| 2. |
- Belmeguenai, Amor, et al.
(författare)
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Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells
- 2010
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 30:41, s. 13630-13643
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Tidskriftsartikel (refereegranskat)abstract
- Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF)-to-Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinaseA (PKA) and case in kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei, but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, nonpotentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output.
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| 3. |
- Bengtsson, Fredrik, et al.
(författare)
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Climbing Fiber Coupling between Adjacent Purkinje Cell Dendrites in Vivo.
- 2009
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Climbing fiber discharges within the rat cerebellar cortex have been shown to display synchrony, especially for climbing fibers terminating in the same parasagittal bands. In addition, Purkinje cells which have the smallest rostrocaudal separation also seem to have the highest degree of synchrony. But this has so far only been investigated for distances down to 250 mum. In the present study, we wanted to investigate whether Purkinje cells that are located immediately next to each other display a particularly pronounced synchrony in their climbing fiber discharges. To this end, we used a previously undescribed type of electrophysiological recording, a single electrode, loose patch, dual dendritic recording, from pairs of adjacent Purkinje cells in the decerebrated, non-anesthetized cat. From each recorded dendrite, this technique provided well isolated, unitary calcium spikes, which we found to have a spontaneous activity that was essentially identical with the pattern of spontaneous climbing fiber discharges. By calculating the coupling in firing between the adjacent dendrites, we found that most climbing fiber responses occurred independently of each other and that the probability of coupled discharges was less than 8%. These values are comparable to those obtained in previous studies for Purkinje cells located within the same parasagittal band and show that climbing fiber coupling within a microzone exists also in non-rodent mammalian species. However, since the degree of synchrony of climbing fiber discharge was not particularly pronounced in adjacent Purkinje cells, it seems unlikely that climbing fiber synchrony has pronounced systematic regional variations within the same microzone.
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| 4. |
- Bengtsson, Fredrik, et al.
(författare)
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Cross-correlations between pairs of neurons in cerebellar cortex in vivo.
- 2013
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Ingår i: Neural Networks. - : Elsevier BV. - 1879-2782 .- 0893-6080. ; 47:Dec.,06, s. 88-94
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Tidskriftsartikel (refereegranskat)abstract
- In the present paper we apply a new neurophysiological technique to make single-electrode, dual loose-patch recordings from pairs of neuronal elements in the cerebellar cortex in vivo. The analyzed cell pairs consisted of an inhibitory molecular layer interneuron and a Purkinje cell (PC) or a Golgi cell and a granule cell, respectively. To detect the magnitude of the unitary inhibitory synaptic inputs we used histograms of the spike activity of the target cell, triggered by the spikes of the inhibitory cell. Using this analysis, we found that single interneurons had no detectable effect on PC firing, which could be explained by an expected very low synaptic weight of individual interneuron-PC connections. However, interneurons did have a weak delaying effect on the overall series of interspike intervals of PCs. Due to the very high number of inhibitory synapses on each PC, a concerted activation of the interneurons could still achieve potent PC inhibition as previously shown. In contrast, in the histograms of the Golgi cell-granule cell pairs, we found a weak inhibitory effect on the granule cell but only at the time period defined as the temporal domain of the slow IPSP previously described for this connection. Surprisingly, the average granule cell firing frequency sampled at one second was strongly modulated with a negative correlation to the overall firing level of the Golgi cell when the latter was modified through current injection via the patch pipette. These findings are compatible with that tonic inhibition is the dominant form of Golgi cell-granule cell inhibition in the adult cerebellum in vivo.
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| 5. |
- Bengtsson, Fredrik, et al.
(författare)
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In Vivo Analysis of Inhibitory Synaptic Inputs and Rebounds in Deep Cerebellar Nuclear Neurons
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal function depends on the properties of the synaptic inputs the neuron receive and on its intrinsic responsive properties. However, the conditions for synaptic integration and activation of intrinsic responses may to a large extent depend on the level of background synaptic input. In this respect, the deep cerebellar nuclear (DCN) neurons are of particular interest: they feature a massive background synaptic input and an intrinsic, postinhibitory rebound depolarization with profound effects on the synaptic integration. Using in vivo whole cell patch clamp recordings from DCN cells in the cat, we find that the background of Purkinje cell input provides a tonic inhibitory synaptic noise in the DCN cell. Under these conditions, individual Purkinje cells appear to have a near negligible influence on the DCN cell and clear-cut rebounds are difficult to induce. Peripheral input that drives the simple spike output of the afferent PCs to the DCN cell generates a relatively strong DCN cell inhibition, but do not induce rebounds. In contrast, synchronized climbing fiber activation, which leads to a synchronized input from a large number of Purkinje cells, can induce profound rebound responses. In light of what is known about climbing fiber activation under behaviour, the present findings suggest that DCN cell rebound responses may be an unusual event. Our results also suggest that cortical modulation of DCN cell output require a substantial co-modulation of a large proportion of the PCs that innervate the cell, which is a possible rationale for the existence of the cerebellar microcomplex.
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| 6. |
- Bengtsson, Fredrik, et al.
(författare)
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Integration of sensory quanta in cuneate nucleus neurons in vivo
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e56630-
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Tidskriftsartikel (refereegranskat)abstract
- Discriminative touch relies on afferent information carried to the central nervous system by action potentials (spikes) in ensembles of primary afferents bundled in peripheral nerves. These sensory quanta are first processed by the cuneate nucleus before the afferent information is transmitted to brain networks serving specific perceptual and sensorimotor functions. Here we report data on the integration of primary afferent synaptic inputs obtained with in vivo whole cell patch clamp recordings from the neurons of this nucleus. We find that the synaptic integration in individual cuneate neurons is dominated by 4-8 primary afferent inputs with large synaptic weights. In a simulation we show that the arrangement with a low number of primary afferent inputs can maximize transfer over the cuneate nucleus of information encoded in the spatiotemporal patterns of spikes generated when a human fingertip contact objects. Hence, the observed distributions of synaptic weights support high fidelity transfer of signals from ensembles of tactile afferents. Various anatomical estimates suggest that a cuneate neuron may receive hundreds of primary afferents rather than 4-8. Therefore, we discuss the possibility that adaptation of synaptic weight distribution, possibly involving silent synapses, may function to maximize information transfer in somatosensory pathways.
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| 7. |
- Bengtsson, Fredrik, et al.
(författare)
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Ketamine and xylazine depress sensory-evoked parallel fiber and climbing fiber responses.
- 2007
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 98:3, s. 705-1697
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The last few years have seen an increase in the variety of in vivo experiments used for studying cerebellar physiological mechanisms. A combination of ketamine and xylazine has become a particularly popular form of anesthesia. However, because nonanesthetized control conditions are lacking in these experiments, so far there has been no evaluation of the effects of these drugs on the physiological activity in the cerebellar neuronal network. In the present study, we used the mossy fiber, parallel fiber, and climbing fiber field potentials evoked in the nonanesthetized, decerebrated rat to serve as a control condition against which the effects of intravenous drug injections could be compared. All anesthetics were applied at doses required for normal maintenance of anesthesia. We found that ketamine substantially depressed the evoked N3 field potential, which is an indicator of the activity in the parallel fiber synapses (-40%), and nearly completely abolished evoked climbing fiber field potentials (-90%). Xylazine severely depressed the N3 field (-75%) and completely abolished the climbing fiber field (-100%). In a combination commonly used for general anesthesia (20:1), ketamine-xylazine injections also severely depressed the N3 field (-75%) and nearly completely abolished the climbing fiber field (-90%). We also observed that lowered body and surface temperatures (<34 degrees C) resulted in a substantial depression of the N3 field (-50%). These results urge for some caution in the interpretations of studies on cerebellar network physiology performed in animals anesthetized with these drugs
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| 8. |
- Bengtsson, Fredrik, et al.
(författare)
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Specific Relationship between Excitatory Inputs and Climbing Fiber Receptive Fields in Deep Cerebellar Nuclear Neurons.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Many mossy fiber pathways to the neurons of the deep cerebellar nucleus (DCN) originate from the spinal motor circuitry. For cutaneously activated spinal neurons, the receptive field is a tag indicating the specific motor function the spinal neuron has. Similarly, the climbing fiber receptive field of the DCN neuron reflects the specific motor output function of the DCN neuron. To explore the relationship between the motor information the DCN neuron receives and the output it issues, we made patch clamp recordings of DCN cell responses to tactile skin stimulation in the forelimb region of the anterior interposed nucleus in vivo. The excitatory responses were organized according to a general principle, in which the DCN cell responses became stronger the closer the skin site was located to its climbing fiber receptive field. The findings represent a novel functional principle of cerebellar connectivity, with crucial importance for our understanding of the function of the cerebellum in movement coordination.
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| 9. |
- Caligiore, Daniele, et al.
(författare)
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Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.
- 2016
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Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230.
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Tidskriftsartikel (refereegranskat)abstract
- Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.
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| 10. |
- Cenci, M. Angela, et al.
(författare)
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On the neuronal circuitry mediating l-DOPA-induced dyskinesia
- 2018
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Ingår i: Journal of neural transmission. - : Springer. - 0300-9564 .- 1435-1463. ; 125:8, s. 1157-1169
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Forskningsöversikt (refereegranskat)abstract
- With the advent of rodent models of l-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.
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